法尼基转移酶和香叶基香叶基转移酶-I的强效抑制剂。

Potent inhibitors of farnesyltransferase and geranylgeranyltransferase-I.

作者信息

Nguyen Diem N, Stump Craig A, Walsh Eileen S, Fernandes Christine, Davide Joseph P, Ellis-Hutchings Michelle, Robinson Ronald G, Williams Theresa M, Lobell Robert B, Huber Hans E, Buser Carolyn A

机构信息

Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.

出版信息

Bioorg Med Chem Lett. 2002 May 6;12(9):1269-73. doi: 10.1016/s0960-894x(02)00154-3.

DOI:10.1016/s0960-894x(02)00154-3

PMID:11965368

Abstract

Compound 1 has been shown to be a dual prenylation inhibitor with FPTase (IC50=2 nM) and GGPTase-I (IC50=95 nM). Analogues of 1, which replaced the cyanophenyl group with various biaryls, led to the discovery of highly potent dual FPTase/GGPTase-I inhibitors. 4-trifluoromethylphenyl, trifluoropentynyl, and trifluoropentyl were identified as good p-cyano replacements.

摘要

化合物1已被证明是一种对法尼基转移酶（FPTase，IC50 = 2 nM）和香叶基香叶基转移酶-I（GGPTase-I，IC50 = 95 nM）的双重异戊二烯化抑制剂。1的类似物，用各种联芳基取代氰基苯基，导致发现了高效的双重FPTase/GGPTase-I抑制剂。4-三氟甲基苯基、三氟戊炔基和三氟戊基被确定为氰基的良好取代基。